Low molecular weight heparins (LMWHs) have received widespread acceptance as the first choice for initial prevention and treatment of venous thromboembolism via subcutaneous injection one to two times daily in the clinic. The need for frequent injections creates barriers to patient compliance, primarily during long-term management. Conjugation of drugs with polyethylene glycol (PEGylation) has been shown to significantly increase the circulating time of therapeutics. In order to develop a LMWH analogue with the extended circulating half-life, PEGylated LMWHs were prepared and characterized as well as their safty and pharmacokintics profiles were evaluated in a cell or a rodent model, respectively.